POTENT INHIBITION OF THE PROINFLAMMATORY RESPONSES OF HUMAN POLYMORPHONUCLEAR CELLS BY PROSTAGLANDIN E-1 BUT NOT BY PGI(2) OR CARBACYCLIN

The effects of prostaglandin E-1 (PGE(1)) on adhesion of activated hum an polymorphonuclear cells (HPMNs) tg human umbilical vein endothelial cells (HUVECs) and on chemotaxis of HPMNs were compared with those of prostaglandin I-2 (PGI(2)) or its chemically stable analog carbacycli n. Although HUVECs treated with PGI(2) inhibited only fMLP-activated H PMN adhesion, both HUVECs and HPMNs treated with PGE(1) equally inhibi ted HPMN adhesion, thus indicating the appropriate reactions to endoth elium-leukocyte interaction by PGE(1). In the presence of a nonspecifi c phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), PGE( 1) inhibited HPMN chemotaxis induced by either fMLP or LTB4 whereas bo th PGI(2) and carbacyclin had no effect. To examine whether the respon se of PMNs to PGs is species-specific, intracellular cAMP accumulation in response to PGs was determined in human, guinea-pig, and rat isola ted PMNs. Although PGE(1) increased cAMP levels in all PMNs tested, bo th PGI(2) ana carabacyclin increased cAMP only in rat PMNs; These resu lts demonstrate that HPMN cAMP formation can be affected by PGE(1) but not by PGI(2). The findings help our understanding of the clinical us e of PGs in patients with peripheral arterial occlusive diseases.